The Role of Immunotherapy in MMR-Deficient Endometrial Carcinoma: State of the Art and Future Perspectives

Abstract

This study provides a comprehensive overview of the role of immunotherapy in the treatment of mismatch repair-deficient (MMRd) endometrial carcinomas. Immunotherapy has emerged as a transformative approach in the treatment of MMRd due to the high mutation rate and subsequent PD-1/PD-L1 overexpression seen in these tumors. This review analyzes the current landscape of existing randomized clinical trials, highlighting the efficacy of immune checkpoint inhibitors (ICIs) like pembrolizumab, avelumab, and dostarlimab. Additionally, the focus extends to the potential of combined therapeutic strategies, such as the integration of ICIs with targeted agents, while also exploring the application of immunotherapy in non-traditional settings beyond advanced or recurrent disease. This includes emerging roles in the adjuvant and neoadjuvant contexts to prevent recurrence and target early-stage disease. These findings underscore the importance of tailoring treatments based on the molecular characteristics of each tumor and paving the way for future advancements in the field of gynecologic oncology. Despite promising results, this article acknowledges the necessity of further research to refine patient selection criteria and explore combination strategies that can overcome resistance mechanisms.

Keywords: MMRd; endometrial cancer; immune checkpoint inhibitors; mismatch repair deficiency; molecular profile; targeted therapy.

Figure 1

Interaction between a T cell and a cancer cell, highlighting key receptor–ligand pairs involved in immune checkpoint regulation. The figure emphasizes the interaction between the PD-1 receptor on the T cell and its ligand PDL-1 on the cancer cell, as well as the CTLA-4 receptor on the T cell. Both the PD-1/PD-L1 and CTLA-4 pathways are targeted by immune checkpoint inhibitors (ICIs), which help to reactivate the immune system’s ability to recognize and attack cancer cells [12]. Created with BioRender.com.